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HIV attacks immune cells The merits of measuring HIV particles in the blood as a way to predict a patient's ability to fight off the disease have been challenged. A study suggests measuring viral load is a much less reliable way to predict loss of key CD4 immune cells than previously thought.

The finding may lead to a rethink on asssessing when to start treatment.

The study, led by Case Western Reserve Univesity, appears in the Journal of the American Medical Association.

The results of this study may have profound implications in our understanding of how HIV causes disease

Dr Benigno Rodriguez

Predicting disease progression is crucial in the treatment of HIV-positive people - in particular the decision about when to start antiretroviral therapy (HAART).

HAART has been credited with saving millions of lives, but it can cause potent side effects, and so doctors do not like to start using it until absolutely necessary.

More complex

Current treatment guidelines advise doctors to measure viral load as one way of assessing when to start treatment.

HIV specifically targets CD4 cells, a type of white blood cell, and as they decline in number the body loses the ability to fight off infection, raising the risk of complications associated with Aids.

The theory is that the higher the viral load, the faster CD4 cells will be lost.

However, the latest study found viral load explains only about 5% of the variation from person to person in the rate of CD4 cell loss.

This suggests CD4 depletion cannot be viewed as a simple consequence of the amount of virus circulating in the blood.

Instead, the findings suggest the factors governing disease progression are rather more complex, and may include damage that HIV is able to inflict on the immune system in an indirect way.

Patient management

Lead researcher Dr Benigno Rodriguez said: "The results of this study may have profound implications in our understanding of how HIV causes disease and in our approach to the management of HIV-infected patients."

The researchers used a sophisticated statistical modeling technique to assess viral load and CD4 cell loss in more than 2,800 patients with HIV who were not receiving treatment.

Edwin Bernard, editor of AIDS Treatment Update, said it was known that CD4 decline varied enormously between people with a similar viral load, and that treatment guidelines had begun to play down the importance of the measure as a diagnostic tool.

"This study provides important new information to help us understand exactly how much viral load can predict the need to start treatment on an individual level."

He said it was clear that a variety of genetic and immunological factors affected an individual's response to HIV infection - and ways to measure these factors would become key.

However, he said the study did not question the value of viral load measurements for assessing how well antiretroviral therapy was working.

Mary Lima, of the HIV charity Terrence Higgins Trust said: "The immune system is very complex, so more research is needed to clarify how the disease progresses and when medication would be most effectively started."

Viral load is a benchmark for monitoring the effectiveness of treatment, not for when to start treatment (CD4's the right one for that). This new study don't say viral load is the wrong way to measure whether treatment is working.

The new study more or less confirms the seminal 1996 MACS study which found that on a group level CD4 decline is faster when viral load is higher. But it points out that looking at the individual this relationship is not so clear and therefore other (maybe unmeasured) immunological, environmental and genetic factors must be in play. I think we, as people with HIV, already know this...

I checked the UK treatment guidelines and the ONLY time viral load is mentioned in the when to start section is this:

"Individuals with CD4 counts 201–350 cells/mm3

It is recommended that the majority of people should initiate therapy with CD4 counts between 200 and 350 cells/mm3. Within this range, the time of initiation in a particular individual may be based upon patient preference, the rapidity of CD4 decline, symptoms, viral load, and co-morbidity such as hepatitis C infection."

Viral load is not mentioned in relation to people with CD4 of 200 or less or more than 350. Not at all. The main criteria in the UK is CD4 count.

I am writing to the BBC cos clearly they's got the wrong end of the UK stick.

Viral loads are important in looking at treatment effectiveness, but the absolute CD4 level has usually been the trigger that indicated it was time to start treatment.

Viral loads can be deceptive. I know people with viral loads between 60,000 and 100,000 who aren't on treatment as yet because their CD4s still remain high and stable.

I have also see the opposite, people with low viral load whose CD4s were in the tank and who were advised to begin treatment.

Many things come into play regarding immune system response and failure, not the least of which is the individual's ability to fight/control the virus on its own.

If there is an adjustment of when treatment is started, I think it should be to increase the CD4 level when it is recommended. I personally believe that anyone whose CD4 count is consistently between 300 to 350 should start treatment.Waiting until the CD4s nose dive below 300 places the person in jeopardy of losing too much of their immunological memory.Of course, that is just my opinion.

However, the latest study found viral load explains only about 5% of the variation from person to person in the rate of CD4 cell loss.

This suggests CD4 depletion cannot be viewed as a simple consequence of the amount of virus circulating in the blood.

Well, I understand that VL is important to see how therapy is working, but follow this logic..

If what is meant by "Therapy is Working" is that there is a reduction in VL, and this study says that VL explains only about 5% of CD4 cell loss is explained by VL, then wouldn't this suggest a different definition of "therapy is working"? It would seem that reducing the VL in the bloodstream is not the only therapy needed.

Well bugger the back buttin, I typed a detailed and well considered response but lost it

So short version: the study is about using viral load to predict when to start treatment, not to monitor whether ARVs are suppressing viral replication. Everyone enrolled on the study was not on treatment, if they went on treatment they were taken out of the study at that point. I agree with it's findings. I don't think it's major news, I think every doc and most folk here know that different viral loads affect each people's HIV infection differently. The study may have implications for US guidelines/decision-making on starting treatment but not in the UK, where CD4 is the benchmark. The BBC re-edited the story so it now reads:

"...More complex

Current treatment guidelines advise doctors that measuring viral load can be one way of assessing when to start treatment for some patients - although in the UK actual CD4 count is deemed to be the most important factor..."

The BBC reporter is a fault for being hasty with the pen, and not checking with a reliable source.

However (ahem) ... Dr Rodriguez' comment used by the BBC, that the "results of this study may have profound implications in our understanding of how HIV causes disease" is a big up me & my science puff, and rubbish. The study's a retrospective stats analysis and confirms what most real-life docs & patients already know: off combo: CD4 important, on combo: viral load important. Clearly there's lots still to find out about HIV, and other things to look at, but for now, this is the state of the clinical science. If this study influences US treatment guidelines away from complex considerations of viral load re: when to start combo, all well and good.

PS - There is, M, in your post a valid long-term concern, which is about how treatment success is judged. For ARV combo it's supressed viral replication + (usually) a consequent increase in CD4 count, but I agree, there's more to the picture, & combo won't forever be the only effective treatment method. - matt

Blondie, cos the only important metric 1 mnth or so after starting treatment with combo is whether yr viral load has dropped... CD4 though is a simple test bloods wise n in the UK it would be routine.

Maestro, the info you are looking for will concern immunological and host (genetic) factors that affect HIV's natural history in a person's body. This is a nose to the journals job cos often it's not reported in detail or widely, but I post below a few starting points.

You won't be lost for long. The tests vary in everyone. You put 'em all together and they paint a picture over time. If the researches had just called me I could've told 'em they could use a better test if they want a much clearer more definitive picture with one test. Nonetheless, the tests we have aren't so bad.

Perhaps you should be happy they're not shoving a huge needle in your gut every 3 months!!!